Speech and language impairments can often be the first manifestation of neurodegenerative diseases such as frontotemporal lobar degeneration, corticobasal degeneration and Alzheimer's disease. When the deficits remain limited to language symptoms for at least two years, the term primary progressive aphasia applies. Characterization of the linguistic, cognitive and anatomical features of patients in this first stage of the diseases could provide critical information for early diagnosis of the underlying etiology of the symptoms. However, speech and language functions are rarely assessed in the setting of dementia clinics. Moreover, data from large-scale, longitudinal clinical and neuroimaging studies of primary progressive aphasia have not been available to help guide clinicians. In this study, we propose to perform a detailed, five-year longitudinal investigation of the linguistic and anatomical features of over 200 patients with primary progressive aphasia. This large cohort will be possible because the UCSF Memory and Aging Center has an internationally renowned program of research in atypical and early-onset dementias. General neuropsychological, neurological, functional and most neuroimaging data will also be collected as part of other ongoing projects at the Memory and Aging Center. We will combine modem cognitive and neuroimaging analysis techniques to isolate the subcomponents of the speech and language system that are affected in progressive aphasia and their corresponding sites of anatomical damage. Our preliminary data from 40 patients already show that specific speech and language deficits correspond to remarkably focal patterns of brain atrophy. We will also follow the progression of the disease for five years, and apply statistical models to investigate how changes in language and anatomical features correlate with each other, with changes in functional impairment and with etiological diagnosis at the end of the study period. Evidence gathered from this research will increase our knowledge about the neural basis of speech and language functions and provide crucial data for the diagnosis of neurodegenerative diseases in their early stages, when treatment can be most effective. [unreadable] [unreadable]